title: Topiramate modulates hippocampus NMDA receptors via brain Ca(2+) homeostasis in pentylentetrazol-induced epilepsy of rats.
abstract: BACKGROUND
  Increase in neuronal Ca(2+), activation of hippocampus N-methyl-D-aspartate receptor (NMDAR) and defects in enzymes such as brain cortex microsomal membrane Ca(2+)-ATPase (MMCA) are thought to play a role in epilepsy. Topiramate (TOP) is a novel drug with broad antiepileptic effect, and its effect on brain cortex MMCA is not known. We investigated effects of TOP on pentylentetrazol (PTZ)-induced MMCA activity and NMDAR subunits in rat brain.
  
  
  METHODS
  Thirty-two rats were randomly divided into four equal groups. The first group and second groups were used for the control and PTZ groups, respectively. 50 and 100 mg TOP were administered to rats constituting the third (TOP50) and fourth (TOP100) groups for 7 days, respectively. At the end of 7 days, all groups except the first received a single dose PTZ. Brain and hippocampus samples were taken at 3 hrs after PTZ administration.
  
  
  RESULTS
  The microsomal MMCA activity was lower in the PTZ group than in control although the MMCA activities were higher in the treatment group than in PTZ group. Brain cortex total calcium levels, the hippocampus NMDAR 2A and 2B subunit concentrations were higher in the PTZ group than in control although their concentrations were decreased by TOP50 and TOP100 administration. Total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations were higher in TOP100 group than in TOP50 group.
  
  
  CONCLUSIONS
  The two doses of TOP modulated MMCA activity, total brain cortex calcium and hippocampus NMDAR 2A and 2B subunit concentrations in the epileptic rats.
authors.affiliation: Department of Neurology, Medical Faculty, Suleyman Demirel University, Isparta, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yilmaz
authors.forename: Mustafa
authors.initials: M
authors.lastname: Naziroğlu
authors.forename: Süleyman
authors.initials: S
authors.lastname: Kutluhan
authors.forename: Nigar
authors.initials: N
authors.lastname: Yilmaz
authors.forename: Vedat Ali
authors.initials: VA
authors.lastname: Yürekli
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Vural
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004827:Epilepsy / Q000378:metabolism*; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects*; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010433:Pentylenetetrazole; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D000077236:Topiramate
chemical_list: D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D000077236:Topiramate; D005632:Fructose; D000252:Calcium-Transporting ATPases; D002118:Calcium; D010433:Pentylenetetrazole